Synthesis and hepatoprotective activity of Mannich base derivatives of silybin
10.16438/j.0513-4870.2017-1200
- VernacularTitle:水飞蓟宾Mannich碱衍生物的合成及保肝活性研究
- Author:
Bao-jun WANG
1
;
Min HAN
2
;
Zhi-yao LI
2
;
Jing CAO
2
;
Gen-bei WANG
2
;
Yi HE
2
;
Zhong-yu DUAN
1
Author Information
1. School of Chemical Engineering, Hebei University of Technology, Tianjin 300131, China
2. TCM Research Center, Tasly Group Co., Ltd., Tianjin 300410, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
silybin derivatives;
structure modification;
Mannich reaction;
biological activity;
relative bioavailability
- From:
Acta Pharmaceutica Sinica
2018;53(5):771-777
- CountryChina
- Language:Chinese
-
Abstract:
Two novel Mannich base derivatives of silybin, SLB-DEA and DHSLB-PIP, were designed and synthesized. All the structures of new Mannich base derivatives of silybin were characterized by 1H NMR and HR-MS. Their protective action against CCl4-induced liver injury in mice were investigated. The changes of alanine aminotransferase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), total cholesterol (TC) and triglyceride (TG) were determined and the histopathological changes in liver tissues were examined. Pretreatment with a higher dosage of DHSLB-PIP (40 mg·kg-1) prevented CCl4-induced liver injury as indicated by the reduced levels of ALT, AST, LDH and TG. Meanwhile, liver histopathological improvement was observed in the model groups. The pharmacokinetics study in rats showed that the relative bioavailability of SLB-DEA and DHSLB-PIP were 172.5% and 259.8% compared with silybin. All the results suggest that SLB-DEA and DHSLB-PIP may protect liver against injury by CCl4 and the relative bioavailability was significantly increased, which is worth of further investigation for their druggability.
